The long-term objective of this project is to investigate the role of helper T cells and their products in the B cell response. Recently, it has become clear that different subsets of helper T cells produce distinct patterns of lymphokines, and that subsets of T cells can also be defined based on their stage of development. The specific aims of this project are to determine the effects of isolated subsets of helper cells on the response of distinct B cell subpopulations and to determine the mechanism by which helper T cells direct B cells to synthesize distinct isotypes of antibody. The experiments are also designed to evaluate the relative contributions of direct interaction with T cells, of lymphokines and of antigen in the response of B cells. The results will help us to understand the difference seen between responses to pathogens and antigen never before encountered by the organism and memory immune responses. These findings will also help us understand how distinct types of immune responses, represented by the production of antibodies of different isotypes, develop and could suggest ways of influencing their development. Such data will also contribute to basic knowledge about the possible effects of lymphokines versus helper T cells which will be important for evaluating the likely efficacy of therapeutic approaches involving lymphokines versus introduction of cells. Finally, a better understanding of the roles played by helper T cells in different functional B cell responses should help provide the basic foundation to help us understand how dysfunction of helpers could contribute to immunodeficiency, autoimmunity and cancer.